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Biomedical subjects

P Riederer

Publications and source records attributed to P Riederer.

At least 379 records · Page 21Linked to original sources
PubMed1990

Reflection of changes in membrane constituents in various regions of Alzheimer brains to differential scanning thermograms.

To test whether changes in basic biochemical membrane constituents were reflected in membrane fluidity measurements, protein, total lipids, triglycerides, lecithin, cholesterol and alkaline phosphatase were determined in frontal cortex, hippocampus, putamen and nucleus basalis Meynert (NbM) of DAT brains and controls and compared to differential scanning thermograms. Biochemical changes were most pronounced in the hippocampus, while thermostability was altered in the NbM and the frontal cortex. The results indicate that changes in protein content, but not in lipid composition were reflected in alterations of thermostability of the brain regions examined.

Aged↗
PubMed1990

Effects of L-deprenyl and amantadine in an MPTP-model of parkinsonism.

Mongolian gerbils of both sexes received a single daily dose of 40 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over 4 consecutive days. On the fifth day the animals were treated with 15 mg/kg i.p. of L-deprenyl or amantadine or the combination of both drugs. At different time intervals (1, 2, 5 hours) the animals were sacrificed. In the caudate nuclei dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured by an HPLC technique. MPTP affected the dopaminergic (HVA -25%) as well as the serotoninergic system (5-HT -54%, 5-HIAA -31%). L-deprenyl and amantadine accumulated DA and 5-HT in the MPTP affected caudates. Synergistic effects of the drug combination could be proven.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Urinary dopamine sulfate: regulations and significance in neurological disorders.

Dopamine-3-O-sulfate (DA-3-O-S) and dopamine-4-O-sulfate (DA-4-O-S) are important end products of L-dopa metabolism. Therefore they may give indications of disturbances in the peripheral metabolism of catecholamines, when measured in urine samples of patients with Parkinson's disease (PD). In addition, information about the reliability of DA sulfatation after L-dopa therapy may be of significance for its role in the elimination of DA from the peripheral nervous system. Although DA-3-O-S appears to be the predominant sulfo-conjugate in urine, there are no changes in PD nor in depression syndrome compared to controls with or without other neurological disorders. By contrast, DA-4-O-S is significantly decreased in de novo PD subjects. However, a similar reduction is notable in patients with other neurological disorders. In depressed persons the loss of this compound was less pronounced as compared to de novo PD. Treatment with combined L-dopa therapy caused increased excretion of DA-3-O-S, while changes in DA-4-O-S were only marginal. It is concluded that urinary DA-3-O-S cannot be used as marker for PD, while DA-4-O-S is significantly reduced in a variety of neurological disorders and in particular in de novo PD. Further studies are necessary to elucidate its role as possible peripheral marker to distinguish preclinical PD and depression syndrome.

Adult↗
PubMed1990

Brain iron and ferritin in Parkinson's and Alzheimer's diseases.

Semiquantitative histological evaluation of brain iron and ferritin in Parkinson's (PD) and Alzheimer's disease (DAT) have been performed in paraffin sections of brain regions which included frontal cortex, hippocampus, basal ganglia and brain stem. The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron. No such changes were observed in the same regions of DAT brains. The increase of iron is evident in astrocytes, macrophages, reactive microglia and non-pigmented neurons, and in damaged areas devoid of pigmented neurons. In substantia nigra of PD and PD/DAT, strong ferritin reactivity was also associated with proliferated microglia. A faint iron staining was seen occasionally in peripheral halo of Lewy bodies. By contrast, in DAT and PD/DAT, strong ferritin immunoreactivity was observed in and around senile plaques and neurofibrillary tangles. The interrelationship between selective increase of iron and ferritin in PD requires further investigation, because both changes could participate in the induction of oxidative stress and neuronal death, due to their ability to promote formation of oxygen radicals.

Aged↗
PubMed1990

Changes in pyruvate dehydrogenase complex (PDHc) activity and [3H]QNB-receptor binding in rat brain subsequent to intracerebroventricular injection of bromopyruvate.

Pyruvate dehydrogenase complex (PDHc), a link between carbohydrate and acetylcholine metabolism, is a regulatory enzyme for glucose and neurotransmitter metabolism in the brain and is reduced in Alzheimer-diseased brain. To study functional consequences of an inhibition of PDHc on muscarinic receptor binding, bromopyruvate, a suicide inhibitor od PDHc, was injected intracerebroventricularly (icv) in rats. Bromopyruvate caused a reduction of PDHc activity in the 3 brain regions examined, however, reaching significance only in the cerebral cortex and the hippocampus and not in the striatum, 24 h after injection. 3, 6, and 12 weeks later, there was a normalization or transiently increased activity, respectively, of PDHc in these brain regions. No changes in concentrations of energy-rich phosphates could be demonstrated in the cerebral cortex 12 weeks after brompyruvate injection. The number of muscarinic receptors was significantly reduced in the cerebral cortex 12 weeks after injection. The data indicate that a transient reduction of brain PDHc activity in vivo is associated with a long-lasting reduction in muscarinic cholinergic receptors. Because comparable changes of PDHc and muscarinic receptors are found in dementia of Alzhemier type, the model of bromopyruvate inhibition of PDHc in rats is suggested to be useful for experimental dementia research.

Alzheimer Disease↗
PubMed1990

Glucocorticoid receptors on mononuclear leukocytes in Alzheimer's disease.

Several lines of evidence suggest disturbances of the hypothalamic-pituitary-adrenal (HPA) system in Alzheimer's disease (AD). In an exploration of the potential role of the glucocorticoid receptor (GR) in AD, GR density and affinity were assessed on mononuclear leukocytes of 12 AD patients and 12 healthy controls. GR binding characteristics did not differ between patients and controls or between patients subdivided according to diagnosis or associated clinical features. These data suggest that the abnormalities of the HPA system in AD are not related to a GR deficiency.

Adrenocorticotropic Hormone↗
PubMed1990

Cholinergic-adrenergic balance: Part 1. Relationship between central and peripheral sensitivities.

Eight healthy volunteers were studied under double-blind conditions after acute challenge with the peripheral beta 2-agonist reproterol, either alone or combined with the peripheral indirect cholinomimetic neostigmine. Their responses were also studied after administration of the centrally active indirect cholinomimetic physostigmine. The beta-adrenergic rise in heart rate was cholinergically suppressed. The beta-adrenergic rise of plasma cyclic adenosine monophosphate (cAMP) was not cholinergically modulated, while that of plasma glucose tended to be cholinergically suppressed. Physostigmine induced an anergic-anhedonic syndrome accompanied by physiological, metabolic, and neuroendocrine stress phenomena. The beta-adrenergic and cholinergic sensitivities, respectively, of the various parameters investigated tended to be nonsignificantly intercorrelated. Only a limited portion of the variance was explained by drug effects. Sensitivity to neostigmine was completely unrelated to sensitivity to physostigmine. Thus, cholinergic sensitivity seems not to be decisive for the fine tuning of the highly complex regulatory systems studied and peripheral sensitivity not to be representative for the central one, at least if unselective drugs like neostigmine and physostigmine are used.

Adult↗
PubMed1990

Cholinergic-adrenergic balance: Part 2. Relationship between drug sensitivity and personality.

Sensitivity to the centrally active cholinomimetic physostigmine varies dramatically among healthy individuals. The elucidation of the reasons for this variability could contribute to the understanding of the pathophysiology of affective disorders where a cholinergic supersensitivity has been demonstrated. Therefore, personality characteristics and habitual stress-coping strategies were related to sensitivity to physostigmine in eight healthy male volunteers. Cardiovascular and behavioral responses tended to be positively correlated with irritability and emotional liability. Passive, "helpless" strategies for coping with stress were positively related to these responses. The metabolic and neuroendocrine responses to physostigmine were generally unrelated to personality. In view of putative beta-adrenergic disturbances in depression, the responses to the peripheral beta 2-adrenergic agonist reproterol were studied. Irritability and emotionality tended to be positively correlated with cardiovascular responses to reproterol as well as with reductions of heart rate by the peripheral cholinomimetic neostigmine.

Adult↗
PubMed1990

Adrenergic-cholinergic imbalances: the physostigmine-syndrome is not antagonized by the MAO-A inhibitor brofaromine.

The centrally active cholinesterase inhibitor physostigmine induces a behavioral syndrome which is thought to represent a model of spontaneous depression. In the present acute trial in 6 healthy volunteers, this model depression was accompanied by clearcut cardiovascular, metabolic and neuroendocrine phenomena of stress. The extent of the changes from baseline, however, scarcely correlated between the behavioral and physiologic phenomena. The behavioral and physiological phenomena could not be antagonized by brofaromine, a putative antidepressant reversibly and selectively inhibiting monoamine oxidase A (MAO-A), contrasting to the complete inhibition by the central cholinolytic scopolamine. This is further evidence that antidepressant efficacy depends on long-term adaptive changes secondary to the enhancement of aminergic neurotransmission rather than this enhancement itself.

Adult↗
PubMed1990

Brofaromine (CGP 11 305 A) in treatment of depression: biological estimation of plasma concentrations.

In an open clinical trial, 13 depressives were treated with the reversible and selective type-A monoamine oxidase (MAO)-inhibitor brofaromine (CGP 11 305 A), the inhibitory potency of deproteinated plasma on a crude MAO preparation from human placenta was measured as a parameter for plasma brofaromine and possibly active metabolites of brofaromine. Patients significantly (p less than 0.01) improved under brofaromine. There were, however, no significant differences in plasma MAO-inhibitory potency between responders (improvement greater than 50%; n = 5) and nonresponders and no correlations with the change from baseline of the total Hamilton Depression Score (HAMD) or with changes of sleep (change from baseline of the HAMD sleep items). MAO-inhibitory potency significantly (p less than 0.05) increased parallel to the increase of the dosage from 50 mg b.i.d. to t.i.d., confirming the validity of this technique. The biological assay applied is a simple and reliable alternative when estimating the plasma concentrations of brofaromine and, possibly, other reversible MAO inhibitors.

Adult↗
PubMed1990

Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia.

The ventral mesencephalons of hamster, guinea pig, cat, monkey, and several humans with and without the diagnosis of schizophrenia were analyzed with in situ hybridization and immunohistochemistry. Extensive codistribution of cholecystokinin mRNA and tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] mRNA was observed in cats and monkeys as well as in all five human subjects with the diagnosis of schizophrenia and in two out of five control brains. Double labeling revealed coexistence of the two markers in cat, monkey, and human. No cholecystokinin mRNA or cholecystokinin peptide was detected in the substantia nigra/ventral tegmental area of the hamster or guinea pig, even after acute and chronic neuroleptic treatment.

Animals↗
PubMed1990

Normal mitochondrial genome in brain from patients with Parkinson's disease and complex I defect.

The mitochondrial genome codes for 13 proteins which are located in the respiratory chain. In postmortem brain of patients with Parkinson's disease, decreased activity of complex I of the respiratory chain could be demonstrated. Because seven subunits of complex I are coded by the mitochondrial genome, we analyzed the mitochondrial DNA of human postmortem substantia nigra, putamen, and frontal cortex by the Southern blot technique. No deletions of the mitochondrial genome could be demonstrated, thus indicating that either subunits which are encoded by the nuclear genome are decreased or enzyme activity is diminished by metabolites, toxins, or increase of Fe3+.

Aged↗
PubMed1990

Circadian rhythms of human pineal melatonin, related indoles, and beta adrenoreceptors: post-mortem evaluation.

Human pineal glands obtained from 77 post-mortem sources from various age groups and times of death were used to examine the 24-hour cycle of serotonin (5-HT), melatonin, N-acetylserotonin (NAS), and beta adrenoceptor density. Pineal glands were divided sagittally and a single half was used to measure 5-HT, NAS, and melatonin concentrations, while the remaining half from the same gland was employed to assess changes in the density of beta adrenoceptors on partially purified membranes. The results show that density of pineal beta adrenoceptors was relatively constant between midnight and 18.00 h and became significantly higher between 18.00 and 20.00 h as measured by ligand saturation binding experiments using (125-I) iodocyanopindolol. The receptor affinity of all of the samples assayed remained in relatively narrow range near 58 pM and only changes in the relative receptor density were apparent. The up-regulation of receptors coincided with an increase in the concentration of 5-HT that began to rise between 16.00 and 20.00 h and became maximal between 20.00 and midnight. NAS, the immediate precursor of melatonin, was also at maximal levels between 20.00 h and midnight. Both 5-HT and NAS began declining after midnight and this change corresponded to the maximal pineal gland concentration of melatonin between midnight and 4.00 h. It is therefore suggested that the up-regulation of beta adrenoceptors noted during the late afternoon and early evening hours corresponds to the increased synthesis of 5-HT and the subsequent conversion to NAS. These events are followed by the highest accumulation of melatonin after midnight and represent the synthesis of melatonin from its precursor NAS in a sequential pattern.

Adolescent↗